title: Nucleotide excision repair proteins rapidly accumulate but fail to persist in human XP-E (DDB2 mutant) cells.
abstract: The xeroderma pigmentosum (XP-E) DNA damage binding protein (DDB2) is involved in early recognition of global genome DNA damage during DNA nucleotide excision repair (NER). We found that skin fibroblasts from four newly reported XP-E patients with numerous skin cancers and DDB2 mutations had slow repair of 6-4 photoproducts (6-4PP) and markedly reduced repair of cyclobutane pyrimidine dimers (CPD). NER proteins (XPC, XPB, XPG, XPA and XPF) colocalized to CPD and 6-4PP positive regions immediately (<0.1 h) after localized UV irradiation in cells from the XP-E patients and normal controls. While these proteins persist in normal cells, surprisingly, within 0.5 h these repair proteins were no longer detectable at the sites of DNA damage in XP-E cells. Our results indicate that DDB2 is not required for the rapid recruitment of NER proteins to sites of UV photoproducts or for partial repair of 6-4PP but is essential for normal persistence of these proteins for CPD photoproduct removal.
authors.affiliation: DNA Repair Section, Dermatology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Kyu-Seon
authors.initials: KS
authors.lastname: Oh
authors.forename: Kyoko
authors.initials: K
authors.lastname: Imoto
authors.forename: Steffen
authors.initials: S
authors.lastname: Emmert
authors.forename: Deborah
authors.initials: D
authors.lastname: Tamura
authors.forename: John J
authors.initials: JJ
authors.lastname: DiGiovanna
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Kraemer
mesh_terms: D018929:Cell Culture Techniques; D004247:DNA; D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics / Q000528:radiation effects*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects; D006801:Humans; D009154:Mutation; D010782:Photolysis / Q000528:radiation effects; D011740:Pyrimidine Dimers / Q000235:genetics / Q000378:metabolism*; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism; D014466:Ultraviolet Rays; D014983:Xeroderma Pigmentosum
chemical_list: C117669:DDB2 protein, human; D004268:DNA-Binding Proteins; D011740:Pyrimidine Dimers; D004247:DNA